DESCRIPTION: This proposal is directed towards understanding the function of a set of genes encoding a family of transcription factors which play a central role in neuronal development. The bHLH proteins comprise a large family of both positive and negative regulators of transcription. The positive regulators fall into two classes: a single common positive regulator is called daughterless, so named for its function in sex determination, forms a heterodimeric complex with proteins from the achaete scute complex. These heterodimers bind to specific regulatory sequences called E box. The negative regulators fall into two classes: The emc protein is an HLH protein devoid of a DNA binding domain. It represses transcription by inhibiting the formation of da achaete/scute heterodimers. The second class including the products of the enhancer of split locus and hairy bind to a distinct set of sequences related to but different from the E box. An elegant set of experiments published by Dr. Caudy in Genes and Development convincingly demonstrate that hairy acts to repress the activity of an achaete/scute target promoter by direct binding to DNA.